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Titolo:
Carbocations in the synthesis of prostaglandins by the cyclooxygenase of PGH synthase? A radical departure!
Autore:
Dean, AM; Dean, FM;
Indirizzi:
Univ Minnesota, Gortner Labs 240, Biol Proc Technol Inst, St Paul, MN 55108 Univ Minnesota St Paul MN USA 55108 Proc Technol Inst, St Paul, MN 55108 Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA Univ Minnesota St Paul MN USA 55108 Evolut & Behav, St Paul, MN 55108 USA Univ Liverpool, Dept Chem, Liverpool L69 3BX, Merseyside, England Univ Liverpool Liverpool Merseyside England L69 3BX , Merseyside, England
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 5, volume: 8, anno: 1999,
pagine: 1087 - 1098
SICI:
0961-8368(199905)8:5<1087:CITSOP>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGHER OXIDATION-STATES; SOLUBLE METHANE MONOOXYGENASE; LEUKOTRIENE A(4) HYDROLASE; MANGANO PROTOPORPHYRIN-IX; H SYNTHASE; ENDOPEROXIDE SYNTHASE; TYROSYL RADICALS; PEROXIDASE REACTION; ARACHIDONIC-ACID; NITRIC-OXIDE;
Keywords:
arachidonic acid; carbocation; cyclization; dioxygenase; hydrogen 1,4-shift; orbital symmetry; prostaglandin G/H synthase; suicide inhibition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
91
Recensione:
Indirizzi per estratti:
Indirizzo: Dean, AM Univ Minnesota, Gortner Labs 240, Biol Proc Technol Inst, St Paul, MN 55108 Univ Minnesota St Paul MN USA 55108 hnol Inst, St Paul, MN 55108
Citazione:
A.M. Dean e F.M. Dean, "Carbocations in the synthesis of prostaglandins by the cyclooxygenase of PGH synthase? A radical departure!", PROTEIN SCI, 8(5), 1999, pp. 1087-1098

Abstract

Evidence already available is used to demonstrate that although prostaglandin G/H synthase hydroxylates arachidonic acid through radical intermediates, it effects cyclizations through a carbocation center at C-10. This is produced following migration of H to the initial radical at C-13 and a 1 epsilon oxidation. Under orbital symmetry control, the cyclizations can give only the ring size acid trans stereochemistry actually observed, After cyclization, the H-shift reverses to take the sequence back into current radical theory for hydroxylation at C-15. Thus 10,10-difluoroarachidonic acid cannot be cyclized, although it can be hydroxylated. Acetylation of Ser516 in the isoform synthase-2 is considered to oppose carbocation formation and/or H-migration and so prevent cyclizations while permitting hydroxylations; theassociated inversion of chirality at C-15 can then readily be accommodatedwithout the change in conformation required by other schemes. Suicide inhibition occurs when carbocations form stable bonds upon (thermal) contact with adjacent heteroatoms, etc. Because the cyclooxygenase and peroxidase functions operate simultaneously through the same heme, phenol acts as reducing cosubstrate for the cyclooxygenase, thus enabling it to promote PGG(2) production and protect the enzyme from oxidative destruction.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 20:06:41